ApoL1, a BH3-only lipid-binding protein, induces autophagic cell death.
We recently reported the identification and characterization of a novel BH3-only pro-death protein, apolipoprotein L1 (ApoL1), that, when overexpressed, induces autophagic cell death (ACD) in a variety of cells, including those originated from normal and cancerous tissues. ApoL1 failed to induce ACD in autophagy-deficient Atg5(-/-) and Atg7(-/-) MEF cells, suggesting that ApoL1-induced cell death is indeed autophagy-dependent. In addition, a BH3 domain deletion allele of ApoL1 was unable to induce ACD, demonstrating that ApoL1 is a bona fide BH3-only pro-death protein. To further investigate regulation of ApoL1 expression, we showed that ApoL1 is inducible by interferon-gamma and tumor necrosis factor-alpha in human umbilical vein endothelial cells, suggesting that ApoL1 may play a role in cytokine-induced inflammatory response. Moreover, we observed that ApoL1 is a lipid-binding protein with high affinity for phosphatidic acid and cardiolipin and less affinity for various phosphoinositides. Functional genomics analysis identified 5 nonsynonymous single nucleotide polymorphisms (NSNPs) in the coding exons of the human ApoL1 structural gene-all the 5 NSNPs may cause deleterious alteration of ApoL1 activity. Finally, we discuss the link between ApoL1 and various human diseases.
Zhaorigetu
Siqin
S
Department of Biochemistry and Molecular Biology, University of New Mexico School of Medicine, School of Medicine, Albuquerque, New Mexico 87131-0001, USA.
Wan
Guanghua
G
Kaini
Ramesh
R
Jiang
Zeyu
Z
Hu
Chien-an A
CA
D000595:Amino Acid Sequence; D000075944:Apolipoprotein L1; D001053:Apolipoproteins / Q000235:genetics / Q000378:metabolism*; D050197:Atherosclerosis / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D001343:Autophagy; D051023:BH3 Interacting Domain Death Agonist Protein / Q000378:metabolism; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism / Q000494:pharmacology; D050356:Lipid Metabolism; D008075:Lipoproteins, HDL / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D020641:Polymorphism, Single Nucleotide; D012559:Schizophrenia / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D014353:Trypanosomiasis, African / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism / Q000494:pharmacology; D014471:Umbilical Veins / Q000166:cytology / Q000187:drug effects / Q000378:metabolism
C108666:APOL1 protein, human; D000075944:Apolipoprotein L1; D001053:Apolipoproteins; D051023:BH3 Interacting Domain Death Agonist Protein; C494814:BID protein, human; D008075:Lipoproteins, HDL; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma